The modulation of anterior pituitary endocrine function by two growth factors, transforming growth factor alpha (TGFalpha) and TGFe will be studied. TGFalpha, a member of the EGF family, was immunolocalized in pituitary cells secreting prolactin and glycoprotein hormones. TGFe, a member of the epithelin/granulin family of proteins, is a mitogen for epithelial and fibroblastic cells and is a chemoattractant for neutrophils and macrophages. TGFe was identified in yet unspecified secretory pituitary cells. Our hypothesis is that the presence of growth factors in specific secretory cells indicates that the primary role of TGFalpha and TGFe in the anterior pituitary is the modulation of pituitary endocrine function rather regulation of proliferation of pituitary cells. To test our hypothesis we will determine the cellular localization of TGFalpha and TGFe in normal human pituitaries and selected adenomas by in situ hybridization (ISH) and immunohistochemistry. Next we will correlate the level of TGFalpha and TGFe production in human pituitary adenomas in culture with the level of specific hormone secretion, and we will attempt to modulate the level of hormone secretion in these cultures by TGFalpha and TGFe. The hormone induction or suppression by TGFalpha or TGFe will be monitored by Northern blot analysis or by RNAse protection assays. Last we will test the mitogenic effect of TGFalpha and TGFe on pituitary adenomas in culture. We hope than this project will contribute to our understanding of regulation of anterior pituitary endocrine function by autocrine or paracrine action of growth factors. The results should also lead to better understanding of pathogenesis of variety of endocrine disorders and of pathogenesis of pituitary adenomas.